Acetic Anhydride → 2-(2-(Hydroxymethyl)-5-nitrophenyl)ethanol

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Reaction Steps

A mixture of 2-carboxymethyl-4-nitrobenzoic acid (13 g, 57.7 mmol), acetic anhydride (5.45 mL, 57.7 mmol) and toluene (130 mL) were heated to reflux for 5 hrs. The solvent was removed under vacuum to yield 6-nitro-isochroman-1,3-dione (compound (10) in Scheme 2) as a yellow solid (10.51 g, 88%). Borane tetrahydrofuran complex (35.6 mL, 1M in THF) was added dropwise over 40 min to a solution of 6-nitro-isochroman-1,3-dione (2 g, 9.66 mmol) in THF (40 mL) at 0° C. The contents were then stirred for 18 hrs at 25° C., cooled to 0° C., quenched with methanol (30 mL), and stirred for 1 hr. The solvents were removed under vacuum, ethyl acetate (30 mL) was added and the organic phase was washed with 10% aqueous hydrochloric acid. The aqueous acidic layer was backwashed with ethyl acetate (30 mL), the combined organic layers were dried with magnesium sulfate, and evaporated under vacuum until approximately 2 mL of ethyl acetate remained. This solution was filtered through silica gel washing with methylene chloride (30 mL) to remove impurities. The silica gel was flushed with ethyl acetate, the solvent was removed under vacuum to give a solid which was slurried in methylene chloride and filtered to afford the title diol as a white solid, 1.38 g , 73%.

Provenance & Evidence